Myeloproliferative and thrombotic burden and treatment outcome of thrombocythemia and polycythemia patients

Abstract

Prospective studies indicate that the risk of microvascular and major thrombosis in untreated thrombocythemia in various myeloproliferative neoplasms (MPN-T) is not age dependent and causally related to platelet-mediated thrombosis in early, intermediate and advanced stages of thrombocythemia in MPN-T. If left untreated both microvascular and major thrombosis frequently do occur in MPN-T, but can easily be cured and prevented by low dose aspirin as platelet counts are above 350 × 10⁹/L. The thrombotic risk stratification in the retrospective Bergamo study has been performed in 100 essential thrombocythemia (ET) patients not treated with aspirin thereby overlooking the discovery in 1985 of aspirin responsive platelet-mediated arteriolar and arterial thrombotic tendency in MPN-T disease of ET and polycythemia vera (PV) patients. The Bergamo definition of high thrombotic risk and its persistence in the 2012 International Prognostic Score for ET is based on statistic mystification and not applicable for low and intermediate MPN-T disease burden in ET and PV patients on aspirin. With the advent of molecular screening of MPN patients, MPN-T disease associated with significant leukocytosis, thrombocytosis, constitutional symptoms and/or moderate splenomegaly are candidates for low dose peglyated interferon (Pegasys^R, 45 μg/mL once per week or every two weeks) as the first line myeloreductive treatment option in JAK2^V617F mutated MPN-T disease in ET and PV patients. If non-responsive to or side effects induced by IFN, hydroxyurea is the second line myelosuppressive treatment option in JAK2^V617F mutated ET and PV patients with increased MPN-T disease burden.

Keywords: Myeloproliferative neoplasms; Essential thrombocythemia; Polycythemia vera; JAK2^V617F mutation; Aspirin; Interferon; Hydroxyurea

Core tip: Spontaneous endogenous erythroid colony formation and low serum erythropoietin (EPO) levels are highly specific for JAK2^V617F mutated essential thrombocythemia (ET), prodromal polycythemia vera (PV), masked PV and classical PV. The quantitation of JAK2^V617F mutation allele burden plays a key-role in the diagnostic work-up and staging of ET, PV and MF patients. The JAK2^V617F mutation allele burden in heterozygous mutated ET is low but high in combined heterozygous - homozygous or homozygous mutated PV. The combined use of JAK2^V617F mutation load, spleen size and pretreatment bone marrow biopsy are of major prognostic significance and therapeutic importance in ET and PV patients. Large Prospective Unmet Need studies are warranted to delineate the natural history and outcome of targeted treatment in MPN patients of various molecular etiology during long-term or life long follow-up.